Anterior cruciate ligament (ACL) injury creates considerable disability and predisposes the knee to the early onset of osteoarthritis. This is a concern because the past two decades has seen an increased participation of women in sports and with this has come a concomitant increase in ACL injuries. The incidence rate of ACL tears is 2 to 9 times greater amongst females in comparison to males;however, there is limited information with regard to the demographic, injury history, hormonal history, anatomic, neuromuscular, and environmental variables that individually or collectively contribute to the risk of suffering an ACL injury. Most of what is known has come from risk factor studies that have focused on selected variables in isolation (e.g. femoral intra-condylar notch width, A-P knee laxity, or phase of menstrual cycle) and consequently it is not surprising that a comprehensive ACL injury risk model has not been established. Our prior research has revealed that the risk model for ACL injury is probably different for females compared to males and this serves as the rational for our investigation, the objective of which is to find the unique combination of risk factors that identify females and males at increased risk of suffering an ACL injury. The hypothesis of our study is: A combination of demographic, injury history, hormonal history, anatomic, neuromuscular, and environmental variables can be used to identify females at increased risk of non-contact ACL trauma, and that a separate combination of these variables can be used to identify males at increased risk of ACL trauma. Initially, we will establish that examiners can measure the potential risk factors in a reliable manner. We will assemble a cohort of collegiate and pre-collegiate athletes and follow them to prospectively accrue ACL injury cases. We will then perform a nested case-control study to identify risk factors for ACL injury. Three controls for each injury case will selected at the time of injury from among teammates who have not been injured at or prior to that time. For subjects that suffer an ACL tear, the potential risk factors that are not modified by the injury will be measured from the injured limb while the factors that are modified by the injury will be measured from the contra-lateral, normal, limb and used to represent the pre-injury condition of the ACL-deficient limb. The same measurements will be obtained on the matched controls. This investigation is significant because it will determine the putative risk factors that identify females and males at increased risk for ACL injury and allow future intervention studies that reduce the incidence of this debilitating injury.